The objective of the proposed research project is to examine the biobehavioral hypothesis relating chromosome changes to impaired mental functioning in the elderly. Specifically, to determine whether or not hypodiploidy and/or other chromosome changes occur more frequently in glial cells of patients with senile dementia of the Alzheimer type than in those without senile dementia. Human brain tissue culturing and chromosome examination will be obtained at autopsy. Goals for the current year included expanding the number of cases of elderly subjects 65 years and older with dementia and younger subjects less than 40 years of age without dementia as well as improving cell identification techniques and initiating cytogenetic analyses. However, appropriate samples were not readily available and tissue specimens from subjects over a wide age range, which would yield important information on chromosome loss in glial cells as a function of age, were accepted for culturing. Primary attempts are still being made to gather tissues from appropriate subjects. Two methods of cell identification are being used in addition to the immunoperoxidase staining for GFA which we have not found to be adequate. These include the analysis of GABA uptake and the microscopic observation of striking morphological alterations of cells treated with db-cAMP. Because of our specific interest in glial cells, cell identification is of utmost importance. This research constitutes an important step in assessing whether or not chromosome changes represent a biological factor which may underlie senile mental changes.